Journal of ethnopharmacology · 2025
Efficacy and mechanism of iridoid glycosides from Gentianella turkestanorum (Gand.) Holub on non-alcoholic steatohepatitis based on RNA sequencing.
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Zheng Dong-Xuan, Ju Bo-Wei, Wen Li-Mei, Xiang Xue-Ying, Xue Tao-Tao, Dai Wu, Liu Jiang-Yun, Hu Jun-Ping, Yang Jian-Hua
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) is an important component of non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide. Gentianella turkestanorum (Gands.) Holub is a traditional monk medicine used for the treatment of hepatitis, and total iridoid glycosides from it (GTI) are the main active substances in the treatment of liver diseases. However, the role and mechanism of GTI in NASH remain unclear.
AIM OF THE STUDY: This study aimed to assess the effectiveness of GTI in treating NASH induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and clarify the underlying mechanisms.
METHODS: The efficacy of GTI against aberrant lipid metabolism was evaluated in vitro in L02 cells and in vivo in a C57BL/6 NASH mouse model. Based on these evaluations in L02 cells and C57BL/6 NASH mice, swertiamarine (SWT) was identified as a potential active component of GTI. RNA sequencing was performed to further explore the therapeutic effects of SWT on the liver. The analysis identified the targeting of key signalling pathways PPARα, p53, and MAPKp38. The therapeutic efficacy of SWT was validated using siRNAs or agonists against PPARα or MAPKp38.
RESULTS: In this study, a combination of ex vivo and in vivo experiments was used to ascertain the mitigating effects of GTI and SWT on NASH. The efficacy was correlated with PPARα, p53, and MAPKp38 pathways, as determined by RNA sequencing. In vitro and in vivo experiments demonstrated that SWT influenced the expression of PPARα, p-p53, Caspase3, Bax, Bcl2, and p-MAPKp38. However, the efficacy of SWT is counteracted when PPARα is inhibited with siRNAs or MAPKp38 is activated with DHC in vitro.
CONCLUSIONS: SWT, a potential active ingredient in GTI, may have a therapeutic effect on abnormal L02 lipid metabolism and NASH in mice by affecting the PPARα/MAPK/p53 signalling pathway. Therefore, SWT holds potential clinical application in the prevention and treatment of NASH.
AIM OF THE STUDY: This study aimed to assess the effectiveness of GTI in treating NASH induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and clarify the underlying mechanisms.
METHODS: The efficacy of GTI against aberrant lipid metabolism was evaluated in vitro in L02 cells and in vivo in a C57BL/6 NASH mouse model. Based on these evaluations in L02 cells and C57BL/6 NASH mice, swertiamarine (SWT) was identified as a potential active component of GTI. RNA sequencing was performed to further explore the therapeutic effects of SWT on the liver. The analysis identified the targeting of key signalling pathways PPARα, p53, and MAPKp38. The therapeutic efficacy of SWT was validated using siRNAs or agonists against PPARα or MAPKp38.
RESULTS: In this study, a combination of ex vivo and in vivo experiments was used to ascertain the mitigating effects of GTI and SWT on NASH. The efficacy was correlated with PPARα, p53, and MAPKp38 pathways, as determined by RNA sequencing. In vitro and in vivo experiments demonstrated that SWT influenced the expression of PPARα, p-p53, Caspase3, Bax, Bcl2, and p-MAPKp38. However, the efficacy of SWT is counteracted when PPARα is inhibited with siRNAs or MAPKp38 is activated with DHC in vitro.
CONCLUSIONS: SWT, a potential active ingredient in GTI, may have a therapeutic effect on abnormal L02 lipid metabolism and NASH in mice by affecting the PPARα/MAPK/p53 signalling pathway. Therefore, SWT holds potential clinical application in the prevention and treatment of NASH.